title: Mucosal tolerance to E-selectin provides protection against cerebral ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  To study the effect of mucosal toleration to E-selectin on cerebral ischemia-reperfusion injury in rats and associated mechanisms.
  
  
  METHODS
  Rats were exposed to intranasal administration of E-selectin or PBS every other day for 10 days (single-tolerization group) or on two tolerization schedules separated by 11 days (booster-tolerization group). Control group received middle cerebral artery occlusion (MCAO) only. MCAO was performed 48 h after the last dose of E-selectin or PBS. After 2 h ischemia and 22 h reperfusion, the rats were killed. We examined the regional cerebral blood flow, neurological testing, frequencies of CD4+ T and CD8+ T lymphocytes in blood, plasma SOD activity, infarct volumes, and mRNA expressions of IL-10, TGF-beta(1), E-selectin, ICAM-1 and LFA-1 in the ischemic brain tissues.
  
  
  RESULTS
  There were 30.25% (P<0.05) decreases of infarction volumes in the E-selectin booster group accompanied by decreased neurological deficit scores compared with PBS group. Compared with PBS-treated rats, CD8-positive cells were significantly decreased (27.4%, P<0.05), CD4-positive cells tended to increase (P>0.05), SOD activity was obviously increased (P<0.05), mRNA levels of IL-10 were markedly increased (21.0%, P<0.05) and TGF-beta(1) showed an upward trend (6.2%, P>0.05), mRNA levels of E-selectin were prominently decreased (28.7%, P<0.01) and ICAM-1 and LFA-1 had downward trends (P>0.05) in E-selectin booster animals.
  
  
  CONCLUSIONS
  Mucosal tolerance to E-selectin after booster tolerization could relieve cerebral ischemia-reperfusion injury and induce ischemia tolerance in Wistar rats. The mechanisms may involve decreased frequencies of CD8+ T cells in blood, increased plasma SOD activity, heightened mRNA expression of IL-10 and lowered mRNA expression of E-selectin in the ischemic hemisphere.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Yun
authors.forename: Liang
authors.initials: L
authors.lastname: Qing-Cheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Lei
authors.forename: Miao
authors.initials: M
authors.lastname: Jia-Yin
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects* / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D013482:Superoxide Dismutase